Regulation of gene expression by dietary fat

Dietary fat is an important macronutrient for the growth and development of all organisms. In addition to its role as an energy source and its effects on membrane Lipid composition, dietary fat has profound effects on gene ex pression, leading to changes in metabolism, growth, and cell differentiatio n. The effects of dietary fat on gene expression reflect an adaptive respon se to changes in the quantity and type of fat ingested. Specific fatty acid -regulated transcription factors have been identified in bacteria, amphibia ns, and mammals. In mammals, these factors include peroxisome proliferator- activated receptors (PPAR alpha, -beta, and -gamma), HNF4 alpha, NF kappa B , and SREBP1c. These factors are regulated by (a) direct binding of fatty a cids, fatty acyl-coenzyme A, or oxidized fatty acids; (b) oxidized fatty ac id (eicosanoid) regulation of G-protein-linked cell surface receptors and a ctivation of signaling cascades targeting the nucleus; or (c) oxidized fatt y acid regulation of intracellular calcium levels, which affect cell signal ing cascades targeting the nucleus. At the cellular level, the physiologica l response to fatty acids will depend on (a) the quantity, chemistry, and d uration of the fat ingested; (b) cell-specific fatty acid metabolism (oxida tive pathways, kinetics, and competing reactions); (c) cellular abundance o f specific nuclear and membrane receptors; and (d) involvement of specific transcription factors in gene expression. These mechanisms are involved in the control of carbohydrate and lipid metabolism, cell differentiation and growth, and cytokine, adhesion molecule, and eicosanoid production. The eff ects of fatty acids on the genome provide new insight into how dietary fat might play a role in health and disease.